Author Topic: Scientists at UT Discover Glycoprotein Envelope to Fight AIDS  (Read 6048 times)

Offline JC Spencer

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Scientists at UT Discover Glycoprotein Envelope to Fight AIDS
« Reply #2 on: July 17, 2008, 03:35:21 PM »
This is a great week for glycomics, the science of sugars.  Glycobiology / glycoproteins are in the News.

Here is an entirely new finding:
Scientists at the University of Texas Discover Glycoprotein Envelope to Fight AIDS.

Read the complete article and additional information on this great scientific discovery at

Thanks for listening,
J. C. Spencer
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Offline JC Spencer

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Scientists at UT Discover Glycoprotein Envelope to Fight AIDS
« Reply #1 on: July 16, 2008, 11:37:55 AM »
Comments by J. C. Spencer

Scientists at the University of Texas have discovered that the glycoprotein envelope on the HIV virus can be manipulated to save the lives of millions of AIDS patients.  This exciting new information brings additional understanding and validity to the years of research in glycomics conducted my good friend H. Reg McDaniel, MD dating back to the late 1980s.

We know that the HIV cannot replicate on its own and must rely on the host cell to reproduce. HIV infects helper T cells with a protein embedded in its envelope called gp120. The gp120 protein binds to a molecule called CD4 on the surface of the helper T cell.  This process initiates a complex set of reactions that transfers the HIV genetic code into the host cell.

Because this is such an important discovery in glycomics, I am referencing a number of abstracts on the gp 120 protein envelope.  See The Endowment for Medical Research NEWS Section for more details.

Now the article:

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Scientists in UT Houston laboratory of Sudhir Paul, Ph.D., may have uncovered a chink the armor of the deadly HIV virus. Pictured from left to right are: Paul, Yasuhiro Nishiyama, Ph.D., and Stephanie Planque. (Credit: Image courtesy of University of Texas Health Science Center at Houston)

Pathologists Believe They Have Pinpointed Achilles Heel Of HIV

Human Immunodeficiency Virus (HIV) researchers at The University of Texas Medical School at Houston believe they have uncovered the Achilles heel in the armor of the virus that continues to kill millions.

The weak spot is hidden in the HIV envelope protein gp120. This protein is essential for HIV attachment to host cells, which initiate infection and eventually lead to Acquired Immunodeficiency Syndrome or AIDS. Normally the body’s immune defenses can ward off viruses by making proteins called antibodies that bind the virus. However, HIV is a constantly changing and mutating virus, and the antibodies produced after infection do not control disease progression to AIDS. For the same reason, no HIV preventative vaccine that stimulates production of protective antibodies is available.

The Achilles heel, a tiny stretch of amino acids numbered 421-433 on gp120, is now under study as a target for therapeutic intervention. Sudhir Paul, Ph.D., pathology professor in the UT Medical School, said, “Unlike the changeable regions of its envelope, HIV needs at least one region that must remain constant to attach to cells. If this region changes, HIV cannot infect cells. Equally important, HIV does not want this constant region to provoke the body’s defense system. So, HIV uses the same constant cellular attachment site to silence B lymphocytes - the antibody producing cells. The result is that the body is fooled into making abundant antibodies to the changeable regions of HIV but not to its cellular attachment site. Immunologists call such regions superantigens. HIV’s cleverness is unmatched. No other virus uses this trick to evade the body’s defenses.”

Paul is the senior author on a paper about this theory in a June issue of the journal Autoimmunity Reviews. Additional data supporting the theory are to be presented at the XVII International AIDS Conference Aug. 3-8 in Mexico City in two studies titled “Survivors of HIV infection produce potent, broadly neutralizing IgAs directed to the superantigenic region of the gp120 CD4 binding site” and “Prospective clinical utility and evolutionary implication of broadly neutralizing antibody fragments to HIV gp120 superantigenic epitope.”

First reported in the early 1980s, HIV has spread across the world, particularly in developing countries. In 2007, 33 million people were living with AIDS, according to a report by the World Health Organization and the United Nations.

Paul’s group has engineered antibodies with enzymatic activity, also known as abzymes, which can attack the Achilles heel of the virus in a precise way. “The abzymes recognize essentially all of the diverse HIV forms found across the world. This solves the problem of HIV changeability. The next step is to confirm our theory in human clinical trials," Paul said.

Unlike regular antibodies, abzymes degrade the virus permanently. A single abzyme molecule inactivates thousands of virus particles. Regular antibodies inactivate only one virus particle, and their anti-viral HIV effect is weaker.

“The work of Dr. Paul’s group is highly innovative. They have identified antibodies that, instead of passively binding to the target molecule, are able to fragment it and destroy its function. Their recent work indicates that naturally occurring catalytic antibodies, particularly those of the IgA subtype, may be useful in the treatment and prevention of HIV infection,” said Steven J. Norris, Ph.D., holder of the Robert Greer Professorship in the Biomedical Sciences and vice chair for research in the Department of Pathology and Laboratory Medicine at the UT Medical School at Houston.

The abzymes are derived from HIV negative people with the autoimmune disease lupus and a small number of HIV positive people who do not require treatment and do not get AIDS. Stephanie Planque, lead author and UT Medical School at Houston graduate student, said, “We discovered that disturbed immunological events in lupus patients can generate abzymes to the Achilles heel of HIV. The human genome has accumulated over millions of years of evolution a lot of viral fragments called endogenous retroviral sequences. These endogenous retroviral sequences are overproduced in people with lupus, and an immune response to such a sequence that resembles the Achilles heel can explain the production of abzymes in lupus. A small minority of HIV positive people also start producing the abzymes after decades of the infection. The immune system in some people can cope with HIV after all.”

Carl Hanson, Ph.D., who heads the Retrovirus Diagnostic Section of the Viral and Rickettsial Disease Laboratory of the California Department of Public Health, has shown that the abzymes neutralize infection of human blood cells by diverse strains of HIV from various parts of the world. Human blood cells are the only cells that HIV infects.

“This is an entirely new finding. It is a novel antibody that appears to be very effective in killing the HIV virus. The main question now is if this can be applied to developing vaccine and possibly used as a microbicide to prevent sexual transmission,” said David C. Montefiori, Ph.D., director of the Laboratory for AIDS Vaccine Research & Development at Duke University Medical Center. The abzymes are now under development for HIV immunotherapy by infusion into blood. They could also be used to guard against sexual HIV transmission as topical vaginal or rectal formulations.

“HIV is an international priority because we have no defense against it,” Paul said. “Left unchecked, it will likely evolve into even more virulent forms. We have learned a lot from this research about how to induce the production of the protective abzymes on demand. This is the Holy Grail of HIV research -- development of a preventative HIV vaccine.”

Major contributors to the research from the UT Medical School include Yasuhiro Nishiyama, Ph.D., and Hiroaki Taguchi, Ph.D., both with the Department of Pathology and Laboratory Medicine, and Miguel Escobar, M.D., of the Department of Pediatrics. Maria Salas and Hanson, both with the Viral and Rickettsial Disease Laboratory, contributed.

The research was funded by the National Institutes of Health and the Texas Higher Education Coordinating Board.

ScienceDaily - July 16, 2008

Related papers supported by BioInfoBank Library
HIV Envelope Protein gp120 :: chemistry

Biomed Khim. ;52 (5):448-57 17180919 (P,S,E,B) Favorite:1
[Study of conformational homology for the HIV-1 gpi20 V3 loop. structural analysis of the HIV-RF and HIV-Thailand viral strains]

Most cited papers:
Nature. 1998 Jun 18;393 (6686):648-59 9641677 (P,S.E,B) Cited:255
Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody.

T Zhu, H Mo, N Wang, D S Nam, Y Cao, R A Koup, D D Ho Aaron Diamond AIDS Research Center, New York University School of Medicine, NY 10016.

The antigenic structure of the HIV gp120 envelope glycoprotein.

R Wyatt, P D Kwong, E Desjardins, R W Sweet, J Robinson, W A Hendrickson, J G Sodroski

A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding.

C D Rizzuto, R Wyatt, N Hernández-Ramos, Y Sun, P D Kwong, W A Hendrickson, J Sodroski

Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding.

Q J Sattentau, J P Moore Academic Department of Genito-Urinary Medicine, University College and Middlesex School of Medicine, London, United Kingdom.

Antibody neutralization and escape by HIV-1.

Xiping Wei, Julie M Decker, Shuyi Wang, Huxiong Hui, John C Kappes, Xiaoyun Wu, Jesus F Salazar-Gonzalez, Maria G Salazar, J Michael Kilby, Michael S Saag, Natalia L Komarova, Martin A Nowak, Beatrice H Hahn, Peter D Kwong, George M Shaw Howard Hughes Medical Institute, University of Alabama at Birmingham, 720 South 20th Street, KAUL 816, Birmingham, Alabama 35294-0024, USA.

A trimeric structural domain of the HIV-1 transmembrane glycoprotein.

M Lu, S C Blacklow, P S Kim Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.

Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes.

P Westervelt, H E Gendelman, L Ratner Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.

Involvement of the V1/V2 variable loop structure in the exposure of human immunodeficiency virus type 1 gp120 epitopes induced by receptor binding.

R Wyatt, J Moore, M Accola, E Desjardin, J Robinson, J Sodroski Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.

Pathogenesis of human immunodeficiency virus infection.

J A Levy Department of Medicine, University of California School of Medicine, San Francisco 94143-0128.
« Last Edit: July 17, 2008, 04:54:36 PM by JC Spencer »